temozolomide in treating young patients with refractory or recurrent leukemia

Conditions: Leukemia

Summary: rationale: drugs used in chemotherapy, such as temozolomide, work in different ways to stop cancer cells from dividing so they stop growing or die. purpose: this phase i trial is studying the side effects and best dose of temozolomide in treating young patients with refractory or recurrent leukemia.

objectives: primary * determine the maximum tolerated dose and recommended phase ii dose of temozolomide in pediatric patients with refractory or recurrent leukemia. * determine the toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. secondary * determine the antitumor activity of this drug in these patients. * determine the biologic activity and mechanism(s) of resistance to this drug in these patients. outline: this is an open-label, dose-escalation, multicenter study. patients receive oral temozolomide once daily on days 1-5. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. projected accrual: a total of 3-36 patients will be accrued for this study within 18-24 months.

Eligibility criteria:
disease characteristics: * histologically confirmed leukemia of any of the following types: * acute lymphoblastic leukemia * acute myeloid leukemia * chronic myelogenous leukemia in blast crisis * refractory or recurrent disease * immunophenotypic confirmation of disease at initial diagnosis or recurrence * more than 25% blasts in the bone marrow (m3) * active extramedullary disease allowed except for leptomeningeal disease * no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * no active cns disease patient characteristics: age * 1 to 21 performance status * karnofsky 50-100% (for patients \> 10 years of age) * lansky 50-100% (for patients ≤ 10 years of age) life expectancy * not specified hematopoietic * wbc \< 30,000/mm\^3 (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator) * platelet count ≥ 20,000/mm\^3 (platelet transfusions allowed) * hemoglobin ≥ 8.0 g/dl (red blood cell transfusions allowed) hepatic * alt ≤ 5 times upper limit of normal (uln) * albumin ≥ 2 g/dl * bilirubin ≤ 1.5 times uln renal * creatinine normal for age or * creatinine clearance or radioisotope glomerular filtration rate ≥ 70 ml/min/1.73 m\^2 other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no uncontrolled infection prior concurrent therapy: biologic therapy * at least 7 days since prior biologic therapy, including immunotherapy * at least 3 months since prior stem cell transplantation * no evidence of active graft-vs-host disease * no concurrent biologic therapy * no concurrent immunotherapy chemotherapy * recovered from prior chemotherapy * at least 6 weeks since prior nitrosoureas * prior therapy with hydroxyurea allowed for up to 24 hours before initiation of study drug * no other concurrent chemotherapy endocrine therapy * concurrent hydrocortisone or other corticosteroids allowed as premedications prior to blood product transfusions in patients with prior severe allergic reactions radiotherapy * recovered from prior radiotherapy * no concurrent radiotherapy surgery * not specified other * no other concurrent anticancer agents * no other concurrent investigational drugs

Keywords: recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia relapsing chronic myelogenous leukemia childhood acute promyelocytic leukemia (m3) blastic phase chronic myelogenous leukemia